• Journal of Pharmaceutical Investigation
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• 제26권2호
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• pp.119-124
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• 1996

To develop oral controlled release dosage forms, ionic interactions between polymers and drugs were evaluated. Hydroxypropylmethyl cellulose and carboxymethylene were used as model nonionic and ionic polymers, respectively. 5-fluorouracil, propranolol-HCl and sodium salicylate were selected as model nonionic, cationic and anionic, respectively. Polymer-drug mixtures were compressed into tablets and drug release kinetics from these tablets were determined. Drug release from the tablets made of the nonionic polymer was not affected by the charge of drugs, rather, was regulated by the solubility of drugs in different pH releasing media. However, drug release kinetics were significantly affected when drug-polymer ionic interactions exist. Enhanced drug release was observed from anionic drug-anionic polymer tablets due to ionic repulsion, whereas drug release was retarded in cationic drug-anionic polymer tablets owing to ionic attractive force. Therefore, the results suggested that the polymer-drug interactions are important factors in designing controlled release dosage forms.

• Journal of Pharmaceutical Investigation
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• 제41권6호
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• pp.347-354
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• 2011

Repeated oral administration of loxoprofen can induce many side effects such as gastric disturbances and acidosis. Therefore, we considered alternative routes of administration for loxoprofen to avoid such adverse effects. The aim of this study was to develop an ethylene-vinyl acetate (EVA) matrix system containing a permeation enhancer for enhanced transdermal delivery of loxoprofen. The EVA matrix containing loxoprofen was fabricated and the effects of drug concentration, temperature, enhancer and plasticizer on drug release were studied from the loxoprofen-EVA matrix. The solubility of loxoprofen was highest at 40% (v/v) PEG 400. The release rate of drug from drug-EVA matrix increased with increased loading dose and temperature. The release rate was proportional to the square root of loading dose. The activation energy (Ea), which was measured from the slope of log P versus 1000/T, was 5.67 kcal/mol for a 2.0% loaded drug dose from the EVA matrix. Among the plasticizer used, diethyl phthalate showed the highest release rate of loxoprofen. Among the enhancers used, polyoxyethylene 2-oleyl ether showed the greatest enhancing effect. In conclusion, for the enhanced controlled transdermal delivery of loxoprofen, the application of the EVA matrix containing plasticizer and penetration enhancer could be useful in the development of a controlled drug delivery system.

• Journal of Pharmaceutical Investigation
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• 제39권6호
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• pp.437-443
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• 2009

To develop a topical bioadhesive formulation of clotrimazole for enhanced transdermal delivery, hydroxypropyl methylcellulose gel containing permeation enhancer was formulated and permeation studies were carried out. The release characteristics of the drug from the gel formulation were examined according to the receptor medium, drug concentration, and temperature. The rate of drug release from the gel increased with increasing drug concentration and temperature. The activation energy (Ea) of drug permeation, which was calculated from the slope of log P versus 1/T plots, was 14.41kcal/mol for a 1%(w/w) loading dose. The enhancer, such as saturated, unsaturated fatty acids, pyrrolidones, propylene glycol derivatives, glycerides, and non-ionic surfactants, were incorporated onto the gels to increase the amount of drug permeation into the skin. Among the enhancers used, polyoxyethylene 2-oleyl ether showed the highest level of enhancement. These results show that clotrimazole gels containing polyoxyethylene 2-oleyl ether could be used for the enhanced transdermal delivery of clotrimazole.

• 폴리머
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• 제27권6호
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• pp.536-541
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• 2003

불포화 폴리(3-히드록시알칸오에이트) (UPHA)를 생합성하고 이 고분자 매트릭스 내에서의 약물방출 경향을 조사하였다. UPHA의 생합성에 사용된 균주는 Pseudomonas oleovorans (ATCC 29347)이고 탄소원은 10-undecenoic acid를 사용하였으며 산-염기조절방법 배취형태 발효법을 이용하여 미생물 배양을 행하였다. 생합성된 UPHA는 $^1$H- 및 $^{13}$C-NMR, FT-IR, GPC 및 DSC 등을 사용하여 물리 및 화학적 분석을 행하였다. 약물방출 실험은 확산셀을 이용하여 모델약물인 케토프로펜의 방출량을 HPLC를 이용하여 측정하였고 UPHA의 가교도, 패취두께, 경피투과 향상제 등의 영향에 대하여 조사하였다. UPHA의 가교도의 증가에 따라 약물방출 속도가 늦어지고 약물방출 속도가 일정해지는 경향을 나타내었다. 경피투과용 패취의 두께가 두꺼워질수록 약물방출 지속시간이 길어지고 경피투과 향상제인 프로필렌 글리콜의 함량 증가에 따라 방출 속도가 향상되는 경향을 나타내었다.

• 대한의생명과학회지
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• 제12권4호
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• pp.443-450
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• 2006

To demonstrate their possibilities as an enhanced vaccine delivery system, protein-loaded Poly lactide glycolide copolymer (PLGA) microspheres were prepared with different physical characteristics. Ethyl acetate (EA) solvent extraction process was employed to prepare microspheres and the effects of process parameters on drug release properties were evaluated. The biodeuadability of microspheres was also evaluated by the pH change and GPC (Gel permeation chromatography). Primary IgG antibody responses in BALB/c mice were compared with protein saline solutions as negative controls and adsorbed alum suspensions as positive controls after single subcutaneous injection for in vivo studies. The microspheres showed a erosion with a highly porous structure and did not keep their spherical shape at 45 days and this result could be confirmed by GPC. In vitro release of proteinous drug showed initial burst effect in all batches of microspheres, followed by gradual release over the next 4 weeks. PLGA microspheres were degraded until 45 days and the secondary structure of OVA was not affected by the preparation method. Enzyme-linked immunosorbent assays demonstrated that the single subcutaneous administrations of OVA-loaded PLGA microspheres induced enhanced serum IgG antibody response in comparison to negative and positive controls. These results demonstrated that microspheres providing the controlled release of antigens might be useful in advanced vaccine formulations for the parenteral carrier system.

• 한국생물공학회:학술대회논문집
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• 한국생물공학회 2005년도 생물공학의 동향(XVII)
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• pp.711-712
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• 2005

• Archives of Pharmacal Research
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• 제28권8호
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• pp.983-987
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• 2005

Hydrogels composed of glycidyl methacrylate dextran (GMD) and poly(acrylic acid, PM) were prepared by UV irradiation method for colon-specific drug delivery. GMD was synthesized by coupling of glycidyl methacrylate to dextran in the presence of 4-(N,N-dimethylamino)pyridine. GMD was photo-polymerized by ammonium peroxydisulfate as initiating system in phosphate­buffered solution (0.1 M, pH 7.4). And then, acrylic acid monomer was added and subsequently heat-polymerized by 2,2'-azobisisobutyronitrile as an initiator. The hydrogels exhibited high swelling ratio (about 20) at $37^{\circ}C$, and showed a pH-dependent swelling behavior. In addition, the swelling ratio of the hydrogel was remarkably enhanced to about 45 times in the presence of dextranase at pH 7.4. The swelling-deswelling behavior proceeded reversibly for the GMD/PM hydrogels between pH 2 and pH 7.4. Release of 5-aminosalicylic acid from the GMD/PAA hydrogels was evaluated in simulated gastrointestinal pH fluids in the absence or presence of dextranase. We concluded that the hydrogels prepared could be used as a dual-sensitive drug carrier for sequential release in gastrointestinal tract.

• 한국응용약물학회:학술대회논문집
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• 한국응용약물학회 1996년도 춘계학술대회
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• pp.282-282
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• 1996

The purpose of this study was to prepare the nifedipine dry elixir (NDE) and coated nifedipine dry elixir (CNDE) containing nifedipine ethanol solution for improving the dissolution rate and bioavailability of nifedipine. NDE containing nifedipine and ethanol in wall materials of dextrin was prepared using a spray-dryer and then NDE was coated with eudragit acrylic resin to make CNDE. Shape and size of the NDE and CNDE were monitored by scanning electron micrograph and laser particle size analyzer In vitro dissolution tests were performed in simulated gastric and intestinal fluid. Bioavailability of NDE and CNDE were compared with drug powder suspension and commercial soft capsule after oral administration of the preparations to rats. NDE and CNDE are spherical in shape. Cross-sectional view of dry elixirs indicates the large inter cavity containing ethanolic drug solution in shell. Geometric mean diameter of NDE and CNDE is about 6.64 and 8.70 $\mu\textrm{m}$, respectively. Drug dissolution rate within first 5 min from NDE increased dramatically irrespective of dissolution medium. However, CNDE showed a particularly retarded dissolution rate in pH 1.2 simulated gastric fluid compared with NDE. The bioavailability of nifedipine in the NDE was increased dramatically compared with drug powder suspension. CNDE reduced initial burst-out plasma peak compared with NDE. CNDE as a sustained release delivery system could reduce the initial burst-out plasma peak due to controlling the release rate of nifedipine from NDE and maintain the effective plasma level over a longer period within therapeutic window with enhanced bioavailability of nifedipine.

• Journal of Pharmaceutical Investigation
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• 제27권3호
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• pp.225-231
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• 1997

For the effective administration of naloxone, we attempted to investigate the naloxone sustained-release implants. Using the biodegradable polymer, poly[(diethyl glutamate)-co-(ethyl glycinate)phosphazenes](PGGP), the implantable devices containing naloxone hydrochloride(NLX HCl) and naloxone base(NLX) were prepared. The release rates of NLX and NLX HCl were compared. Influences of NLX contents on release rates were examined. For pharmacokinetic studies, NLX and NLX HCl loaded devices were implanted subcutaneously in rabbits and then the plasma concentrations of NLX were determined by HPLC(ECD). NLX-containing devices were implanted with various doses and pharmacokinetic parameters according to dose were calculated. The relative bioavailabilities were evaluated and compared. Incorporation of NLX in the polymer leaded to a slow release. There were no differences of release rates based on drug contents. In pharmacokinetic parameters determined in 216 hours, NLX loaded devices resulted in enhanced bioavailability with the higher AUC (p<0.01) than NLX HCl loaded devices and MRT was significantly (p<0.05) increased. This result demonstrates that NLX is more suitable for sustained release devices than NLX HCl. Therefore it is anticipated that the effective concentrations of naloxone could be maintained for longer periods and bioavailabilities could be improved by naloxone sustained-release implants, with varying drug base/hydrochloride.

• Journal of Pharmaceutical Investigation
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• 제32권4호
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• pp.299-303
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• 2002

The oral bioavailability of itraconazole is variable and low in fasting state. This is mainly due to the low solubility of this drug. Bioavailability can be improved by changing the formulation and it is general that the liquid preparations show greater bioavailability than the solid dosage forms such as tablets and capsules do. Benzyl alcohol-water binary mixture showed the excellent solubilizing capacity for itraconazole but the release of the drug from the preparation needs to be enhanced. In this study, various nonionic surfactants and hydrophilic polymers, poloxamers, were screened to investigate their effects on the releasε of itraconazole from the liquid preparations. Poloxamer 407 showed the most enhancing effect on the drug release and the release rate was proportional to thε amount of poloxamer 407 added. A liquid preparation of itraconazole, consisting of benzyl alcohol/water/poloxamer 407 ternary solvent system, releasεd more than 80% of the total drug amount at 5 min and showεd the possibility of a new formulation development.